生物谷综合：微小RNA (microRNA，简称miRNA)是生物体内源长度约为20－23个核苷酸的非编码小RNA，通过与靶mRNA的互补配对而在转录后水平上对基因的表达进行负调控，导致mRNA的降解或翻译抑制。到目前为止，已报道有几千种miRNA存在于动物、植物、真菌等多细胞真核生物中，进化上高度保守。
一般而言，编码miRNAs的基因最初产生一个长的pri-RNA分子，这种初期分子还必须被剪切成约70-90个碱基大小、具发夹结构单链RNA前体（pre-miRNA）并经过Dicer酶加工后生成。然而近期发表在Genes & Development（1月1日）的三篇独立文章在果蝇中发现了一种双向性转录（bidirectionally transcribed）microRNA，这也许提示了一种新机制，对于了解miRNA功能的多样性来说意义重大。
在头两篇文章中，来自纽约约斯隆/凯德琳癌症研究中心（Memorial Sloan-Kettering Cancer Center）发育生物学系的赖教授（Eric C. Lai，2007年获得NHGRI果蝇及线虫研究项目190万美元资助，生物谷注）领导的研究团队和麻省理工学院的Manolis Kellis领导的研究小组分别发现Hox miRNA位点的反义转录（antisense transcription）：miR-iab-4能产生一种新的miRNA前体——mir-iab-8，继而成为有调控活性的RNAs。
反义转录，其产物就是与正义的RNA互补的反义RNA(或者称反义转录本)，反义RNA可以通过与正义RNA的互补结合实现转录后基因沉默，从而控制基因表达。在这里发现的反义转录产物mir-iab-8在异位表达（ectopical expressed，生物谷注）的时候，可以通过直接抑制Hox基因靶标产生同源异性表型（homeotic phenotype，生物谷注）。
而在第三篇文章中，来自哈佛医学院的Welcome Bender博士则证明了miR-iab-4的敲除揭示了一种从相反链转录的miRNA的存在，而且反义miRNA的缺失会引起一个hox基因的些轻微去抑制（derepression）。
这些在果蝇和哺乳动物中发现的额外的反义miRNA说明这种新机制也许能增加科学家们对miRNA功能的多样化的了解。
在07年11月份的《Cell》上，来自瑞士日内瓦大学细胞生物学系的研究人员也发现了一种不依赖于RNAi（RNA干扰）的基因沉默机制：他们在酿酒酵母中发现反义RNA稳定（Antisense RNA Stabilization）能通过组蛋白去乙酰化引起转录基因沉默。这些研究都进一步揭示了生物体中基因沉默的多样化。
生物谷推荐英文原文：
原文一：
GENES & DEVELOPMENT 22:26-36, 2008
Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci
David M. Tyler1, Katsutomo Okamura1, Wei-Jen Chung1, Joshua W. Hagen1, Eugene Berezikov2, Gregory J. Hannon3, and Eric C. Lai1,4
1 Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10021, USA; 2 Hubrecht Institute, Utrecht 3584 CT, The Netherlands; 3 Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
Many microRNA (miRNA) loci exhibit compelling hairpin structures on both sense and antisense strands; however, the possibility that a miRNA gene might produce functional species from its antisense strand has not been examined. We report here that antisense transcription of the Hox miRNA locus mir-iab-4 generates the novel pre-miRNA hairpin mir-iab-8, which is then processed into endogenous mature miRNAs. Sense and antisense iab-4/iab-8 miRNAs are functionally distinguished by their distinct domains of expression and targeting capabilities. We find that miR-iab-8-5p, like miR-iab-4-5p, is also relevant to Hox gene regulation. Ectopic mir-iab-8 can strongly repress the Hox genes Ultrabithorax and abdominal-A via extensive arrays of conserved target sites, and can induce a dramatic homeotic transformation of halteres into wings. We generalize the antisense miRNA principle by showing that several other loci in both invertebrates and vertebrates are endogenously processed on their antisense strands into mature miRNAs with distinct seeds. These findings demonstrate that antisense transcription and processing contributes to the functional diversification of miRNA genes.
[Keywords: BX-C; antisense; homeotic gene; microRNA]]
Received September 13, 2007; revised version accepted November 6, 2007.
4 Corresponding author.
E-MAIL laie@mskcc.org ; FAX (212) 717-5604.
